Leukaemia Flashcards
What is the definition of acute lymphoblastic leukaemia?
Malignant disease of primitive lymphoid cells (lymphoblasts).
Who does ALL most typically affect?
Most common childhood cancer (peaks age 2-4)
Can affect adults over 45
Often associated with Down syndrome
What is the pathophysiology of ALL?
Malignant change in one of the lymphocyte precursor cells causing acute proliferation of a single type of lymphocyte (usually B lymphocytes)
Excessive proliferation of these cells causes them to replace the other cell types being created in the bone marrow, leading to pancytopenia
What are some clinical features of ALL?
Marrow failure - anaemia, infections, bleeding
Leukaemic effects - high count with obstruction of circulation
Involvement of areas outside the marrow and blood (extramedullary) eg CNS, testis
Bone pain
What are some investigations for ALL?
Blood count and film:
- Reduction in normal cells
- Presence of blasts (large size, high nuclear:cytoplasmic ratio, prominent nucleus)
Coagulation screen
Bone marrow aspirate:
- Morphology
- Immunophenotype
- Cyto/molecular genetics
- Trephine
What is the management of ALL?
Multi-agent chemotherapy for 2-3 years
CNS targeted treatment
Hickman line used for long term central venous access
What are some complications of ALL and AML disease?
Anaemia
Neutropenia (gram negative bacteria and fungal infections)
Thrombocytopenia (bleeding, purpura, petechiae)
What are some complications of ALL and AML treatment?
Nausea and vomiting
Hair loss
Liver and renal dysfunction
Infection
Late effects: loss of fertility, cardiomyopathy
What is the definition of acute myeloid leukaemia?
Malignant disease of the primitive myeloid cells (progenitor cell for granulocytes, monocytes, erythrocytes or platelets).
Who does AML typically affect?
Elderly (>60 years)
Often associated with myelodysplastic syndromes but can arise ‘de novo’
What are some clinical features of AML?
Marrow failure: anaemia, infections, bleeding
Subgroups characteristic presentation
- Coagulation defect/DIC in acute promyelocytic leukaemia
- Gum infiltration in acute monocytic leukaemia and acute myelomonocytic leukaemia
What are some investigations of AML?
Blood count and film:
- Reduction in normal size
- Presence of blasts (large size, high nuclear:cytoplasmic ratio, prominent nucleolus)
- Auer rods inside blast cell cytoplasm
Coagulation screen
Bone marrow aspirate:
- Morphology
- Immunophenotype
- Cyto/molecular genetics
- Trephine
What is the management of AML?
Multi-agent chemotherapy
- 2-4 cycles
- Prolonged hospitalisation
- Targeted treatments in subsets
- Hickman line used for long-term venous access
What is the definition of chronic myeloid leukaemia?
Malignant proliferation of primitive myeloid cells (granulocytes and their precursors and other lineages eg platelets) with preserved maturation
What is the genetic mutation involved in CML?
Philadelphia chromosome
Translocation between chromosome 9 and 22, t(9:22), resulting in new gene BCR-ABL1
BCR-ABL1 is a tyrosine kinase and causes abnormal phosphorylation leading to haematological changes in CML
What are the three phases of CML?
Chronic:
- Lasts around 5 years, often asymptomatic, diagnosed with incidental raised WBC
Accelerated:
- More symptomatic with anaemia, thrombocytopenia, immunocompromised, 10-20% proportion of blast cells in marrow and blood
Blast:
- Severe symptoms and pancytopenia, often fatal, >30% proportion of blast cells in marrow and blood
What are some clinical features of CML?
Asymptomatic
Splenomegaly
Hypermetabolic symptoms
Gout (high cell turnover causes high urate)
Others: hyperleucocytosis, priapism
What are some investigations for CML?
FBC:
- Normal or decreased Hb
- Increased WBC
- Low/normal/raised platelets
Blood film:
- Neutrophilia with myeloid precursors and blasts
Leucocyte alkaline phosphate (LAP):
- Usually reduced
Bone marrow biopsy:
- Not usually done but would show increased cellularity
Genetics:
-FISH used for cytogenic abnormality in bone marrow or blood
What is the management of CML?
Stem cell/bone marrow transplant in chronic phase (fatal without)
Tyrosine kinase inhibitors (imatinib)
What is the definition of chronic lymphocytic leukaemia?
Chronic proliferation of a single type of well differentiated/less primitive lymphocyte (usually B lymphocytes).
Who does CLL typically affect?
Adults over 55
What are some symptoms of CLL?
Often asymptomatic
Infections, anaemia, bleeding, weight loss
Warm autoimmune haemolytic anaemia
What are some investigations for CLL?
Blood count:
- Hb normal or low
- Increased WBCs
- Normal or low platelets
Blood film:
- Increased lymphocytes (>5x109/L)
- ‘Smear’ or ‘smudge’ cells
Bone marrow:
- Immunophenotyping (mainly CD19/20 and CD5 B cells)
- Cytogenetics (deletion of 13q most common, trisomy 12)
What is the management of CLL?
Chemo not usually need in early stage disease
Absolute indications for treatment:
- Weight loss >10% over 6 months
- Night sweats lasting >1 month
- Progressive marrow failure
What are some complications of CLL?
Can transform into high-grade lymphoma
